The most well-known type of pluripotent stem cell is the embryonic stem (ES) cell. However, the generation of embryonic stem cells can only be derived from embryos, and it has so far not been feasible to create patient-matched embryonic stem cell lines. Induced pluripotent stem (iPS) cells are a type of pluripotent stem cell that can be generated directly from somatic (differentiated) cells. Since iPS cells can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line. iPS cells may be generated through the ectopic expression of Oct 4, Sox2, Lkf4, and c-Myc (OSKM) transcription factors in somatic cells (Takahashi and Yamanaka, 2006), leading to global epigenetic changes during reprogramming (Papp and Plath, 2013). Chromatin regulatory proteins mediate epigenetic remodeling during iPS cell formation, and loss-of-function studies have shown that Polycomb proteins are potent regulators of cell fate reprogramming (Onder et al., 2012). However, iPS cells may retain epigenetic signatures of their somatic cell of origin (Kim et al., 2010; Polo et al., 2010) that can persist through extended passaging (Kim et al., 2011), and the molecular mechanisms responsible for epigenetic memory are unclear.
In ES cells, long noncoding RNAs (lncRNAs) associate with chromatin regulators such as Polycomb proteins (Guttman et al., 2011; Zhao et al., 2010; Zhao et al., 2008) and are required to repress lineage-specific genes in the pluripotent state (Guttman et al., 2011). LncRNAs have been shown to target chromatin regulatory complexes throughout the genome in various developmental settings (Lee and Bartolomei, 2013; Rinn and Chang, 2012), but relatively little is known about lncRNAs in the context of cellular reprogramming.